Hemophilia is a common bleeding disorder (occurring in approximately 1:10,000 males) in which causes severe internal bleeding that often leads to death because the patient's blood doesn't clot normally. Hemophilia usually is inherited with patients displaying severe uncontrollable bleeding events beginning at birth and re-occurring throughout the individual's life. Although there are several types of clotting factors that work together with platelets to help the blood coagulate, people with hemophilia usually have quantitative or qualitative defects in the proteins that encode coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) that prevent normal hemostasis.
Hematopoietic stem cells differentiate in the bone marrow to form megakaryocytes that mature and break-up into several thousand small fragments known as platelets, which in normal conditions circulate quietly (not interacting with the other blood cells or the vessel wall) in the blood stream for approximately 10 days with the main job to become activated, change shape and stick to damaged blood vessel to repair the injury. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and close breaks on the vessels to stop bleeding.
People with hemophilia A are missing or have low levels of clotting factor VIII. About 9 out of 10 people who have hemophilia have type A. People with hemophilia B are missing or have low levels of clotting factor IX. Both clotting factors are normally synthesized in the liver although there are reports that other cell types can be induced to synthesize fully functional forms of recombinant FVIII and FIX proteins.
Hemophilia can be mild, moderate, or severe, depending on how much normal functional clotting factor is present in the blood. About 7 out of 10 people who have hemophilia A have the severe form of the disorder.
Hemophilia usually occurs in males because Factors VIII and IX are located on the X chromosome (although with rare exceptions females who inherit a defective X chromosome each from an affected father and mother who is a carrier for the disease). About 1 in 10,000 individuals are born with hemophilia each year all over the world.
The main treatment for hemophilia is protein replacement therapy. Concentrates of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) can be isolated from pools of donor blood or recombinant protein that has been prepared from tissue culture cell lines transformed with the normal genes encoding FVIII or FIX that are slowly dripped or injected into a vein at the onset of a serious bleeding event. These infusions help replace the clotting factor that's missing or low.
Complications of replacement therapy include developing antibodies response to the normal therapeutic protein that is foreign to the patient's immune system (known as inhibitor formation), which ultimately leads to inactivation or destruction of the clotting factor and uncontrolled bleeding in about 30% of patients, developing viral infections from human clotting factors (from blood contaminated with HIV or Hepatitis from infected blood donors especially in third world countries), very expensive costs of the replacement protein which has a very short half-life (days) which requires frequent re-administration to subside a severe vascular injury and damage to joints, muscles, or other parts of the body resulting from delays in treatment.
Thus, new treatments for hemophilia that overcome these complications are needed.